The NIEHS Biometry and Risk Assessment Program (BRAP) and Toxicology Research and Testing Program (TRTP) have developed a research effort aimed at establishing mechanisms to utilize data on oncogene activation and expression together with dose-response studies for tumor induction in risk analysis of specific classes of chemical carcinogens. Specific aims are: 1) To examine oncogene activation in spontaneously arising tumors in animals and to compare with oncogene activation in chemically-induced tumors to distinguish the mechanistic development of the tumors. 2) To examine the tissue and chemical selectivity for oncogene activation in chemically-induced tumors derived from the NTP carcinogen bioassay program and other animal model systems for chemical carcinogenesis. 3) To characterize oncogene activation and expression in early stages of tumor development. 4) To utilize data on oncogene activation and expression together with dose-response relationships for tumor induction in low dose extrapolation of carcinogenic data. To obtain our research goals, it is necessary to examine animal model systems related to those used in NTP carcinogen bioassay studies and in in-house studies and to extend previous studies for additional information. The basic requirement of this proposal is to obtain tumor and/or preneoplastic tissue for analysis of oncogene activation and/or expression and in some cases to establish dose- response relationships for tumor induction by chemicals.